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Time-keeping mechanisms of embryonic cell cycles

胚胎细胞周期的计时机制

基本信息

批准号：
9287251
负责人：
Stefano Di Talia
金额：
$ 32.53万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9287251
关键词：
Address Biochemical Biochemical Process Biosensor Body part Cell Cycle Cell Cycle Regulation Cell Proliferation Cell Proliferation Regulation Cell division Cells Characteristics Chemicals Chromosome abnormality Computing Methodologies Data Development Developmental Biology Disease Drosophila genus Embryo Embryology Embryonic Development Ensure Enzymes Feedback Gene Expression Genetic Genetic Transcription Genome Genomic Instability Goals Growth Image In Vitro Lead Malignant Neoplasms Measures Messenger RNA Methodology Mitosis Modeling Molecular Molecular Biology Molecular Genetics Morphogenesis Noise Organism Outcome Pathway interactions Phosphotransferases Physics Process Production Regulation Role Signal Transduction Signaling Protein System Testing Time Tissues Transcription Coactivator Transcriptional Regulation Work blastomere structure event cycle experimental study gastrulation genetic approach genetic manipulation in vivo in vivo imaging insight interdisciplinary approach mathematical model novel photo switch protein degradation spatiotemporal theories

项目摘要

During embryonic development each body part is programmed to contain an accurate number and arrangement of cells. This accuracy is achieved through precise regulation of cell proliferation in the face of the molecular noise characteristic of the biochemical processes regulating the cell cycle. The molecular mechanisms by which embryos suppress noise remain poorly understood. Uncovering these mechanisms is a central goal of Developmental Biology and requires the development of novel methodologies to measure quantitatively cellular dynamics in living embryos. The overarching goal of this proposal is to reveal the molecular mechanisms that ensure accurate control of the cell cycle during Drosophila embryonic development. We will study the molecular mechanisms ensuring precise temporal regulation of cell division through control of gene expression, signaling and protein degradation. We have developed live imaging and computational approaches to quantify the dynamics of the major enzymes regulating the cell cycle during embryonic development. In Aim 1, we will use biosensors for the activities of of Cdk1 and Chk1 to identify how chemical waves act to synchronize mitosis in the syncytial embryo. In Aim 2, we will use live imaging to dissect the molecular mechanisms that ensure the cell cycle remodeling at the maternal-to-zygotic transition. In Aim 3, we will elucidate how transcriptional regulation of cdc25string ensures precise regulation of the timing of mitosis during gastrulation. These experiments will define a novel quantitative framework for uncovering how the cell cycle is regulated accurately during embryonic development.

在胚胎发育过程中，身体的每一部分都被编程为包含一个准确的数字，细胞的排列。这种准确性是通过精确调节细胞增殖来实现的，调节细胞周期的生化过程的分子噪音特征。分子胚胎抑制噪音的机制仍然知之甚少。揭示这些机制是一个发展生物学的中心目标，并要求发展新的方法来衡量活胚胎中的定量细胞动力学。该提案的总体目标是揭示确保果蝇胚胎期细胞周期精确控制的分子机制发展我们将研究确保细胞分裂精确时间调节的分子机制通过控制基因表达、信号传导和蛋白质降解。我们开发了实时成像技术，计算方法来量化的主要酶的动态调节细胞周期的过程中，胚胎发育在目标1中，我们将使用生物传感器检测Cdk 1和Chk 1的活性，以确定Cdk 1和Chk 1是如何被激活的。化学波作用于合胞体胚胎中的同步有丝分裂。在目标2中，我们将使用实时成像来解剖确保细胞周期重塑的分子机制在母体到合子的过渡。在Aim中 3，我们将阐明cdc25string的转录调控如何确保精确调控的时间，原肠胚形成期间的有丝分裂。这些实验将定义一个新的定量框架，以揭示细胞周期在胚胎发育期间被精确地调节。